Field of the Invention
This invention relates broadly to a structure for insertion in the anterior mammalian eye for treatment related to natural, predictable aging changes. More particularly the invention relates to a surgically implanted device for the human eye. The device provides structural support to specific ocular anatomy as a means to counteract changes naturally brought about by aging.
Description of the Related Art
All human eyes go through physical changes as a result of the noiinal aging processes. These changes affect various structures of the eye. The human eye has three chambers. The largest is the vitreous chamber. It is filled with the gelatinous material of the vitreous body. This material fills the eye and principally serves to maintain the shape of the eye. It also plays a role in accommodation to anchor the posterior lens attachments and interact with induced forces. In front of the vitreous chamber are the posterior and anterior chambers. These chambers also play a role in maintaining the shape of the eye through the mechanism of balancing the production and drainage of aqueous humor. This fluid fills both chambers, which are separated by the iris. The pupil is the area of communication between the two chambers. The aqueous humor is produced by the ciliary body in the posterior chamber and then circulates forward through the pupil to the anterior chamber. The fluid then slowly filters through the annular structure of the trabecular meshwork and its distal system. The anterior chamber is demarked by the cornea and iris. The boundaries of the posterior chamber are the iris and anterior lens capsule. The posterior chamber peripherally reaches to the ciliary body, which is the location of the musculature and apparatus attachment responsible for accommodation.
Accommodation involves constriction and relaxation of the ciliary muscles to achieve the control of focus. The process of accommodation is naturally controlled by the brain. It is an automatic process that results in clear vision by manipulation of the lens shape and position to focus light on the retina. The eye goes through a predictable degradation of accommodation with aging. The focusing apparatus becomes progressively more flaccid over time. The musculature and feedback mechanism remain intact, but the ability to actuate change and focus diminishes throughout life, until it is essentially totally ineffective. This process is known as presbyopia. The youthful eye has excessive ability to accommodate in the order of tenfold of what is generally required. This surplus erodes over time, and usually reaches the threshold of being initially problematic at 40 to 45 years old. The degradation continues to progress and usually renders the eye with complete inability to sustain any near focus by the age of 60. This is a very relevant juncture with respect to the aging process of the eye and subsequent prevalence of various disease processes as they manifest. These predictable changes result in an anterior shifting of the lens and focusing apparatus. The lens and apparatus are attached by micro ligaments known as zonules. The zonules become progressively more flaccid with aging. The cause of this increased flaccidity is likely two fold. The zonules simply stretch over time due to perpetual use. This stretching is likely a contributing factor, but aging changes to the actual lens is responsible for the majority of change. These aging changes eventually manifest as cataracts. Cataract development is a predictable and understood change to the aging eye. The matrix of the crystalline lens becomes cloudy and impairs vision. This typically becomes problematic enough to require cataract surgery between the ages of 70 to 80. As part of the process the lens stiffens, thickens, and subsequently increases in diameter. This increase in diameter results in outward displacement of the zonule attachments. The entire focusing system becomes relatively slack and displaces forward. The thickening of the lens also compounds these forward forces as the vitreous body pushes the structures from behind. Surgically removing the cataract becomes necessary and is common practice.
At the stage prior to surgery, the intact aged eye has to maintain function with very unfavourable displaced and compressed anatomy. The prevalence of various eye diseases begins to increase dramatically after the first five decades of life. These diseases include, but are not limited to, glaucoma, Fuchs' corneal dystrophy, and retinal detachments. These three diseases are discussed herein, as each disease relates to forward shifting anatomical changes. Presbyopia and refractive error are also discussed, but are not considered to be diseases.
Glaucoma is a disease which is diagnosed by evidence of vision loss or measured change to the optic nerve and the retinal nerve fiber layers. It is estimated that over 4 million Americans have glaucoma, but only half of the people who suffer from the disease are aware of their condition. Approximately 120,000 people are blind as a result of the disease. Glaucoma is the second leading cause of blindness in the world. Estimates put the total number of suspected cases of glaucoma at about 70 million worldwide. Glaucoma is a group of diseases that relate to intraocular pressure (IOP) and the aqueous humor fluid dynamics of the eye. It is a balance between the rate of aqueous production from the ciliary body in the posterior chamber and drainage via the trabecular meshwork and its distal system located in the anterior chamber. It is estimated that the ciliary body produces aqueous at an average rate of 2-3 micro liters per minute which translates into about 1.5 liters per year. There are variations in rates of production; however, these fluctuations are likely not as significant as the ability to drain the fluids, to balance pressure. The aging of the eye results in a predictable anterior shift of the structures posterior to the trabecular meshwork. This shift results in restriction of flow based on the structural change. Evidence of this shift is observed clinically when a cataract is surgically removed. On average, there is a 17% decrease in intraocular pressure (IOP), shortly after surgery. The anterior chamber angle instantly widens upon removal of the lens. The structure of the trabecular meshwork is able to open under these favourable changes. The trabecular meshwork is a mesh-like structure of tapering pores that direct the fluids into Schlemm's canal. The natural architecture of this porous tissue cannot perform its function well under compression. Glaucoma patients often undergo cataract surgery prematurely to take advantage of the drop in baseline IOP. Cataract surgery could be delayed or avoided in many cases where the need for the operation is driven by the pressure reduction aspects. The visual complications of natural aging cataracts are generally noticed by one's early sixties. Vision continues to decline typically requiring cataract surgery at ages ranging from early to mid seventies. The average life expectancy in the United States from birth is 78. It is more relevant to consider that the average life expectancy from an age of 63 is 20 years. Thus, a significant portion of the population does not live long enough to require cataract surgery based on vision needs.
Although glaucoma is a group of diseases, it can generally be classified into two categories: closed angle and open angle glaucoma. Closed angle glaucoma is a medical emergency when the angle is truly closed. This occurs when the peripheral iris occludes the trabecular meshwork. Topical and systemic pharmaceutical agents must be employed and often an emergency iridotomy is needed. An iridotomy involves making puncture-like openings through the iris without the removal of iris tissue. It is performed either with standard surgical instruments or a laser. The iridotomy allows for instant equalization of IOP between the anterior and posterior chamber.
Primary Open Angle Glaucoma (POAG) accounts for the majority of glaucoma cases. It presents with an apparently open drainage structure and often normal intraocular pressures. It is characterized by progressive optic neuropathy resulting in atrophy of the optic nerve and the nerve fiber layers. The disease process must have factors that are not apparent upon superficial anatomical observation and clinical IOP measurements. It is well documented that IOP fluctuates. Animal studies where IOP measuring probes have been implanted have demonstrated very dramatic results. Rabbit and monkey subjects produced IOP spikes in the order of 90 mmHg. This represents pressure almost six times normal values. This highlights the necessity of IOP clearing time for these spikes to maintain eye health. The eye must be able to sustain brief spikes in IOP. Sneezing and rubbing one's eyes would be examples of normal acute IOP spikes. Early POAG cases are likely, in part, the inability of the eye's drainage system to facilitate a safe pressure clearing time. In these open angle cases the trabecular meshwork structure would be initially compressed internally and out of superficial view. This coincides with the stage of rapid decline in loss of accommodation at the age of 50 to 60. This directly correlates to the age where the incidence of glaucoma dramatically increases. The angle is internally compressing in the periphery as the ciliary body and its structures shift forward. The angle and whole anterior chamber are narrowing. The farther forward the structures shift, the greater the zonular flaccidity. As this progresses there is less pulling on the anatomy adjacent to the trabecular meshwork, which is known to decrease IOP. The action of pilocarpine eye drops utilizes this mechanism to lower IOP. Pilocarpine also acts on the ciliary muscle and causes it to contract. When the ciliary muscle contracts, it opens the trabecular meshwork through increased tension on the scleral spur at the base of the trabecular meshwork. This narrowing trend becomes more apparent 10 to 20 years later with significant cataract development. The central thickening of the lens produces additional forward movement that is more evident on clinical observation.
In general the disease process is treated by isolated approaches to certain aspects of the disease. Pharmaceutical agents represent the primary form of treatment. They work on modulating production or drainage of the aqueous fluids. These therapies are hindered by costs, compliance and side effects. Managing drug side effects in an elderly population is difficult.
Tissue modifying procedures without device implantation have traditionally been secondary or complimentary approaches to the pharmaceuticals. These surgical procedures include trabeculectomy and laser trabuculoplasty. Trabeculectomy is very invasive surgery with considerable side effects. Scarring of the treated area is the greatest risk for failure. Antimetabolite and antineoplastic medications are often needed to augment the procedure. Other risks include infection, haemorrhaging, cataract formation, and hypotony. With hypotony, if the pressure remains too low for prolonged periods maculopathy and possible vision loss my result. Laser trabuculoplasty is more widely utilized because of its less invasive nature. Both procedures have very limited success and usually still require chronic paramedical use All procedures which involve surgical trauma to compromised tissues must contend with the tissue's natural healing mechanism. The early positive response often renders a compromised eye at greater risk for failure. There is a shift now to improved surgical procedures as a primary treatment. An effective single procedure has the potential to reduce costs and eliminate compliance issues. Most devices available as treatments are focused on by-passing or bridging elements of the drainage pathway. The development and improvement of glaucoma shunts or stents remains a very active field of investigation. The ultimate goal is to have a single surgical procedure as a first line treatment. There are various shunt designs that continue to evolve. The basic principle is to bypass the resistance of the trabecular meshwork and allow flow of the aqueous humor directly into the Schlemm's canal. If the shunt can remain clear, the pressure in the anterior chamber will remain equalized with the pressure in Schlemm's canal. From there on, the uveoscleral outflow pathway remains intact to modulate IOP. The surgical implantation of such a small stent requires the extreme precision of a skilled surgeon. It is also difficult to be confident that the stent has penetrated the tissues as required to be effective. The lumen of the stent must remain open. The risk of scarring and blockage will always be of concern for patency.
All glaucoma treatments and variations of treatments have notable disadvantages and limited success. Medication has significant side effects and surgery results in tissue trauma. In both cases, the cost of treatment is high. The average direct cost of glaucoma treatment ranges from $623 per year for patients in the earliest stages and in excess of $2,500 a year for end stages of the disease. The annual total costs for glaucoma are approaching $3 billion in the U.S. economy alone. Procedural short term benefits can often result in additional costs associated with failure and complications. A true treatment for glaucoma is a common goal. The drainage systems of the eye may be best left intact if it is possible to provide assistance to circumvent the degenerative process. Trauma and scarring will inevitably compound the regenerative process. Implantation of a device to provide structural support offers promise. It may be possible to cure glaucoma through proactive prevention. Stem cell activity and cellular regeneration in the trabecular meshwork also are likely involved. A device to stimulate the responsible stem cells along with structural support could provide the eye with all that is necessary to prevent the manifestation of glaucoma.
Fuchs' Corneal Dystrophy is a group of degenerative diseases of the corneal endothelium. The endothelium is a monolayer of specialized, flattened, mitochondria-rich cells that line the internal surface of the cornea. Fuchs' dystrophy is clinically observed as an accumulation of focal outgrowths called guttae which are a thickening of the Descemet's membrane. This results in corneal edema leading to decreased vision and potentially vision loss. It is estimated that 5-10% of the population over 50 years old have clinically significant manifestation of the disease. The underlying cause is a deficiency of corneal endothelial cells. The density of endothelial cells on the posterior surface of the corneal predictably decline with aging. There has been significant research and discovery in the genetics of Fuchs' variants. There are early and late onset variations, and women tend to be more affected at an early stage. The common link to all is the decline in endothelial cell density. Evaluation of the endothelium by specular microscopy can demonstrate classic changes of Fuchs' endothelial dystrophy. With the background of the invention in mind, discussion will focus on the corneal endothelium and its role. The principal physiological function of the corneal endothelium is to allow nutrients from the aqueous humor to diffuse into the superficial layers of the cornea, while at the same time actively pumping water out of the cornea back into the anterior chamber. Thus, the corneal endothelium effectively keeps the cornea from becoming edematous and losing clarity. Treatment options vary depending on severity of symptoms and state of disease progression. Early treatments are targeted at reducing the edema. These treatments include topical dehydrating agents, warm air to increase evaporation, lowering IOP, and topical nonsteroidal anti-inflammatory drugs. Treatment is necessary until it is not possible to preserve good vision; at that point keratoplasty is necessary. Penetrating keratoplasty (PK) has been the standard for treatment of Fuchs' endothelial dystrophy. PK involves replacement of the full corneal thickness with donor tissue, even though only the endothelial layer is defective. In recent years, major advances in this field have made replacement of only the endothelial layer possible, without disturbing normal anterior structures of cornea using endothelial keratoplasty. Both are effective procedures, but often have complications and limited duration of effectiveness. Approximately 10% of those identified with the dystrophy will need keratoplasty. The purpose of transplantation is to increase endothelial cell density and thus restore function. As a result, a procedure that allows the eye to regenerate its own endothelial cells may be an effective treatment option. Recently the stem cells responsible for this have been located in the posterior limbus. At this junction between the cornea and sclera, there is an area known as the transition zone where stem cells believed to be responsible for endothelial and trabecular meshwork cells reside. Schwalbe's Line demarks part of the transition zone. The stem cells have been observed to be stimulated after laser trabuculoplasty for glaucoma treatment. Stein cells are known to be activated by trauma. In these cases, the stimulation can be beneficial or detrimental if over stimulated. Mechanical forces are also known to trigger stem cell differentiation. The mechanical stimulation model may be very significant with respect to corneal endothelium regeneration. The link to a decline in endothelial cell density and age may very well be correlated to a decline in accommodative ability. By the age of 45, approximately half of our endothelial cells and most of the ability to accommodate have been lost. A child has potentially ten times more accommodative ability than necessary. Such excessive power to focus would translate into significant forces induced by the ciliary muscles and accommodative apparatus. The transition zone where the stein cells are located absorbs some of these forces. It would be logical to expect certain level of cellular activity to result. Implantation of a device to induce mechanical forces to the transition zone would have the potential to stimulate stem cells. The device will need to provide an appropriate amount of stimulation by means of variable forces and contact area with the transition zone. If a healthy population of endothelial cells can be maintained, Fuchs' dystrophy should not manifest. The underlying genetic predisposition will still exist, but induced mechanical stimulation has the potential to prevent the disease symptoms from manifesting.
Retinal Detachments are generally categorized into idiopathic, traumatic, advanced diabetic, and inflammatory disorders. The majority of disorders fall into the idiopathic classification. This grouping of spontaneous retinal detachments dramatically increases after the age of 40 and peaks at about the age of 60. The bulk of these idiopathic detachments are vitreoretinal in origin. The vitreous humor changes in consistency with aging. Its boundaries shrink away from the retina. This separation is known as a posterior vitreous detachment (PVD). As the vitreous separates, it can pull the retina with it in areas of excessive adhesion. The incidence of retinal tears resulting from a PVD varies on average between 5% and 15%, depending on the presentation. The process of the PVD can be asymptomatic or symptomatic with photopsia. Flashes or sparks of light in the absence of true light are indicative of tension at retinal adhesions and present with greater risk. The symptoms usually subside once the process resolves. Floaters may remain after the process is complete. In the event that the adhesions does not release, a retinal detachment is likely to occur. Retinal detachments of this etiology have a particularly strong correlation with the decline in accommodative ability. It is known that the ciliary body remains active even with lack of any sustainable accommodation. The feedback mechanisms to accommodate also remains, but the cortical stimulation to accommodate is met with a lack of response that ultimately can produce an over active muscular response of the accommodative apparatus. The vitreous body and the zonular attachments have a significant role in the apparatus. There is debate over what is responsible for the ability to accommodate. The exact combination of actions and reactions is not important for the discussion of retinal detachment associated with PVD's. What is significant is the balance of forces. When the ciliary body contracts it relaxes the circumferential lenticular zonules. These include the equatorial, anterior, and posterior zonular limbs. The area of traction exists along the anterior hyaloid of the vitreous body. There are hyaloid zonules that anchor here and ultimately transfer forces to retinal adhesions. The dramatic increase in retinal detachment must have some relation to the actions of the complex accommodative mechanism. When the eye has adequate accommodative control, there is a balance between ciliary contraction and relaxation. The accommodative mechanism would predominately be in a relaxed state, when viewing beyond a few feet. Effectively this state puts tension on the lenticular zonule complex, pulling the lens back and relieving tension on the retinal attachments. The opposite is true of the response to near focus. The ciliary body contracts releasing tension on the lenticular zonule attachments. The vitreous body and its gelatinous characteristics push the lens forward to accommodate. The forward movement is retained by tension transferred around the anterior hyaloid and retinal attachments. With presbyopia the concern is how the feedback mechanism responds to a lack of focus. The action and reaction do not balance and cause instability. The ciliary body easily can go into spasm under these circumstances. These spasms can clinically present as ocular pain. The ciliary muscle may very well become stronger as accommodative ability diminishes with aging. The retinal adhesion will be put under significant traction resulting in the inevitable PVD and risk of retinal detachment. The relationship is complex and it is difficult to isolate the components of the accommodative mechanism. Other tissue related changes with aging must also be factors.
Retinal tears and detachments are treated by a variety of procedures. Success of treatment is high if the detachment is treated in a timely manner. When tears are seen clinically there are generally two approaches, laser photocoagulation and cryopexy. Both methods essentially scar the tissue around the tear to stabilize it. Retinal detachments have more involved surgical treatments. Pneumatic retinopexy is the least invasive. The procedure involves injecting a gas bubble in the eye to float the retinal back in place where it can reattach. Photocoagulation or cryopexy are then used to stabilize any holes or tears. Scleral buckling surgery is another surgical procedure. The surgeon places a piece of silicone sponge, rubber, or semi-hard plastic on the outer layer of the eye and sews it in place. This relieves traction on the retina, preventing tears from proceeding to detachments, by supporting the retina. The most invasive treatment is a vitrectomy. This procedure involves removal of the vitreous body from the eye. Vitrectomy gives the surgeon better access to the retina to repair holes and close large tears.
A procedure that could restore a functional amount of accommodation could reduce retinal traction by stabilizing contraction of the ciliary muscles. The feedback would be restored and the accommodative system would predominately be in a state that relieves tension on the vitreous base and retina. To achieve this reduction in retinal traction, the anterior displacement of the whole system must be returned to a more posterior position. This repositioning could be achieved through careful calculated sizing and implantation of a device to provide structural support and targeted appositional forces.
Refractive Error Correction encompasses a variety of approaches to achieve clear vision. All eyes have a need for visual assistance by optical or surgical procedures during a life time. Emmetropia is the most common presentation. This is a state of vision when one requires no optical aids to see clearly when distant viewing. These individuals have no need for correction until presbyopia sets in at mid life. This loss of accommodative ability is true of all eyes regardless of distance refractive status. The non emmetropic eyes can be divided into myopia or hyperopia, respectively nearsighted or farsighted eyes. Astigmatism is generally present in variable amounts. This represents an unequal curvature of the cornea or internal lens of the eye. There are infinite variations in refractive error and many treatment options available. The most common treatments include spectacles and contact lenses. Essentially all refractive errors can be treated by variations of these solutions. There are many other refractive modification procedures available. Mostly these treatments are elective lifestyle procedures, but in some cases medically necessary. Cataract surgery is an example of necessary surgery. Cataract extraction is the most common surgical procedure in the United States. There are two types of cataract surgery commonly employed today. Standard extracapsular cataract extraction involves removal of the lens in one piece along with the front portion of the lens capsule. This procedure is still utilized, but in limited circumstances due to the larger more invasive incision needed. Phacoemulsification small incision cataract surgery is essentially the standard of care. The surgery utilizes ultra sound energy to fragment the lens so it can be evacuated through the small incision port. The technique employs a foldable posterior chamber interocular lens (PCIOL) to facilitate transplantation through the small incision. The PCIOL is positioned in the remaining lens capsule structure and centrally positioned by flexible haptics. This small incision technique has generally replaced other procedures. It is noted that there are a wide variety of PCIOL's available in various designs and materials. Surgeons have significant surgical liberties in the cataract extraction field. Foldable anterior chamber interocular lenses (ACIOL) have recently been developed. These lenses are employed by the same small incision technique. They are placed in the anterior chamber and positioned by flexible haptics resting in the anterior chamber angle. ACIOL's are generally designed to be used in phakic eyes as they are positioned in the chamber anterior to the lens. This is usually an elective procedure to correct high or difficult prescriptions. The procedure is resorted to when other refractive devices or surgical options are not possible or have limited potential.
The market for elective refractive surgery is well established. Refractive surgery without device implantation includes: Radial Keratotomy (RK), Astigmatic Keratotomy (AK), Photo-Refractive Keratectomy (PRK) and Laser Assisted In-Situ Keratomileusis (LASIK). RK and AK involve carefully placed superficial incisions into the corneal stroma in a radial fashion. These procedures are not performed anymore, and are predecessors that led to PRK and LASIK. The utilization of lasers with PRK and LASIK has much greater control and predictable outcomes. Modern PRK and LASIK are considered elective procedures. They can correct most naturally occurring refractive errors. These are not truly reversible techniques because tissue is removed with the laser.
The implantation of interocular lenses accounts for nearly all of the devices implanted to correct refractive errors. The laser surgery techniques dominate the tissue altering procedures by re-shaping the cornea. Intra-stromal corneal rings are an alternative option for low levels of myopia and astigmatism. Small incisions in the corneal stroma are made. Two crescents or semi-circular shaped ring segments are implanted on opposing sides away from the central cornea. The embedding of the rings in the cornea has the effect of flattening the cornea and changing the refraction. Intacs are the FDA approved device for this procedure. They are made of a relatively rigid material, Poly(methylmethacrylate) (PMMA). Intacs have not gained significant market share despite being marketed as a reversible procedure. Presently they are often used for the treatment of Keratoconus. Their semi-rigid structure offers support to a structurally failing cornea. There is extensive data from photorefractive surgery and cornea curvature altering proceeds. The cornea has an average refractive power of 45 diopters. This high power along with 18 diopters from the natural lens is required to focus light to produce images at the 24 mm axial length of the eye. The majority of naturally occurring refractive errors are within a prescription of one diopter. This is a very small amount with respect to the total power of the system. A device with the ability to internally expand along the corneal base would flatten corneal curvature resulting in decreased myopia. The cornea only requires a flattening of 75 microns to achieve a one diopter decrease in myopia. Achieving such a flattening of the cornea would only require an increase in diameter of 60 microns at the corneal base.
The loss of accommodative ability remains one of great interest within the field of refractive correction. The ability to change focus provides the optical system control and an advantage over any static approach. The development of a device to rejuvenate the natural ineffective aged system is being actively perused. The advantages of such a system could be more significant than the visual control and clarity. Stability of the accommodative musculature has the ability to relieve the retinal tension by returning the system to equilibrium. Present techniques and procedures under investigation to restore accommodation are either external or internal to the posterior chamber. Externally there are techniques that suggest the suturing of bands around the eye to increase the diameter and provide a more rigid external base for the ciliary muscles internally. The concept is to reduce flaccidity of the zonular complex by external expansion to enable some reaction to the accommodative actions of the ciliary muscles.
However, the eye is dynamic and changes in refractive status do have predictable patterns as well changes that cannot be anticipated. In theory, the eye cannot be static until it is aphakic after cataract surgery. At this stage there is no effective accommodation. The cortical connections and accommodative musculature still remain, but no lens remains to facilitate a response. Developing a way of utilizing the cortical and muscular system to facilitate accommodation will be of great benefit. An artificial lens is required to achieve this. Focusing PCIOL's are in development and are already available. The lens is implanted in the posterior chamber replacing the natural lens. The concept is to have a lens with shape changing characteristics to harness the movement of the ciliary muscle during accommodative stimulation. These lenses will continue to develop, but presently have limited success. Harnessing accommodative forces in the anterior chamber would allow for the development of a shape changing lens implant in front of the iris.